Microfluidic devices and systems

ABSTRACT

The present invention is generally directed to improved microfluidic devices and systems, and particularly to a microfluidic device which comprises a planar body structure, at least a first channel network comprising intersecting channels disposed within the body structure wherein the first channel network is contained within an area of the planar body structure that is less than about 6 cm 2 ; and a holder assembly configured to receive the body structure, the holder assembly having at least one aperture disposed therethrough from an upper surface to a lower surface thereof, and wherein the body structure is fixedly mounted to the holder assembly.

CROSS REFERENCE TO RELATED APPLICATION

This application is a continuation of U.S. patent application Ser. No.09/190,428, filed Nov. 12, 1998, U.S. Pat. No. 6,048,498, which is acontinuation of U.S. patent application Ser. No. 08/906,441, filed Aug.5, 1997, now U.S. Pat. No. 5,876,675.

BACKGROUND OF THE INVENTION

Microfluidic systems have been previously described for carrying out anumber of operations, including, e.g., capillary electrophoresis (Manzet al., J. Chromatog. 593:253-258 (1992)), gas chromatography (Manz etal., Adv. In Chromatog. 33:1-66 (1993)), cell separations (U.S. Pat. No.5,635,358) and the like. Generally, such devices have been described inthe context of proof-of-concept experiments, where they have been usedin operations primarily performed by highly skilled technicians. Despitethe advancements made with respect to these devices, however, suchdevices have not been adapted for use by less sophisticated operators.

In particular, the microfluidic devices and systems for controlling andmonitoring the devices described to date, have generally included bulky,complex and expensive prototypical systems whose use requires complexseries of operations and or a high level of skill on the part of theoperator. Further, such systems are generally fabricated in the lab,where time and funding can be at a premium, resulting in little or noattention being given to features of the device that are notspecifically directed to the fluidic elements. As such, these devicestend to be extremely sensitive to operator handling, and by implication,operator error. It would therefor be desirable to provide microfluidicdevices and/or systems which are more “user friendly,” i.e., moreresistant to operator error, and particularly, operator handling error.The present invention meets these and other needs.

SUMMARY OF THE INVENTION

The present invention generally provides improved microfluidic devices,apparatus and systems which reduce the potential for errors which arisefrom operator mishandling of such devices. In particular, the presentinvention provides microfluidic devices which comprises a substratehaving a first surface and at least one edge, at least two intersectingmicroscale channels disposed in the substrate, and a detection window inthe first surface which permits transmission of an optical signal fromat least one of the at least two intersecting channels. These devicesalso comprise a manual handling structure attached to the substrate forhandling the microfluidic device substantially without contacting thefirst surface of the substrate. Also provided are apparatus forutilizing these devices, which apparatus include electrical controlsystems for applying an electric field across each of the at least firstand second intersecting channels within the device, as well as opticaldetectors disposed adjacent to the detection window within the devicefor receiving the optical signal.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 schematically illustrates an embodiment of a microfluidic deviceincorporating a manual handling structure.

FIG. 2 schematically illustrates an alternate embodiment of amicrofluidic device incorporating a manual handling structure.

FIGS. 3A, 3B, and 3C schematically illustrates a further embodiment of amicrofluidic device incorporating a manual handling structure (fromperspective, top, and bottom views, respectively).

FIG. 4 illustrates an ornamental design for a microfluidic device, whichalso incorporates a manual handling structure.

DETAILED DESCRIPTION OF THE INVENTION

The present invention is generally directed to improved microfluidicdevices and systems, and particularly, microfluidic devices that areeasier to handle by the operator, without damaging, contaminating orotherwise fouling, as a result of manual contact with the device.Specifically, the present invention provides microfluidic devices andsystems which include manual handling structures, for allowing easyhandling of the small scale devices with minimal potential for foulingas a result of manual contact with the device. As noted above,previously, microfluidic devices have been used mainly in “proof ofconcept” applications, by highly skilled researchers for extremely lowthroughput applications, e.g., single sample separations etc. Because ofthe nature of this use, it has been largely unnecessary to providemicrofluidic devices with elements to reduce or prevent operator erroror mishandling. Specifically, because such devices were used by highlyskilled researchers, the chances of their becoming damaged by operatorerror or mishandling were reduced. Similarly, because these devices hadbeen used primarily in such “proof-of-concept” research, e.g., involvinglow throughput or single sample assays, they were generally considereddisposable, somewhat obviating the need for significant barriers tomishandling and the like.

The microfluidic devices according to the present invention, on theother hand, are generally intended to be used by the ordinary researchand development consumer, e.g., laboratory technicians, physicians inpoint of care diagnostic applications, in home testing, and the like. Assuch, the devices must generally be designed to withstand or prevent acertain level of consumer mishandling. Of particular relevance ismishandling due to excessive contact with the microfluidic device by theoperator. For example, because microfluidic devices include channelshaving extremely small cross-sectional dimensions, e.g., regularly inthe range of from 1 to 15 μm, these devices are extremely vulnerable tofouling as a result of dirt, dust or other particulate matter which canbe deposited in the reservoirs of the device and potentially block oneor more of the channels of the device.

Further, in addition to fouling the interior portions of these devices,direct contact by a user with the surface of the microfluidic device canhave a number of additional adverse effects. For example, the devices ofthe present invention typically include a detection window for observingor optically detecting the results of the operation of the device, e.g.,assay results. Often such optical detection methods rely upon highlysensitive instruments, detectors and the like. Accordingly, anyinterference resulting from the collection of dirt or oils on thisdetection window can adversely effect the amount or quality of thesignal that is transmitted by the window and detected by the detector.

Similarly, collection of dirt and oils on the surface of themicrofluidic devices can provide surface locations at which moisture maycondense during the operation of the device. Such moisture andcondensation can provide an avenue for the contamination of the device,or cross contamination among the various fluid access ports or wells ofthe device. Further, and perhaps more critically, the formation of thiscondensation on the surface of an microfluidic device which employs anelectrokinetic-based material transport and direction system can alsolead to electrical shorting between adjacent reservoirs/electrodes usedin these systems, e.g., as used in preferred aspects of the presentinvention. Such shorting can significantly reduce and even destroy theefficacy of these material direction and transport systems.

The problems associated with handling the microfluidic devices arecompounded by the small size of these devices. In particular, becausethe microfluidic devices described herein have relatively small externaldimensions, it is substantially more difficult to handle such deviceswithout contacting large portions of the surface of the device. Further,improvements in fluid direction systems, e.g., electroosmotic systems,have permitted a substantial reduction n the size of microfluidicdevices. As these devices shrink in size, it becomes more and moredifficult to handle them, without contacting a substantial portion oftheir surfaces, potentially leading to the problems described.

By providing a means of manually handling or holding the device withoutcontacting the surface of the device in which the reservoirs aredisposed, one can substantially reduce the probability that dirt or dustmight find its way into the reservoirs and channels of the device. Suchdust and dirt can readily foul microfluidic channels which typicallyinclude at least one cross sectional dimension as small as 0.1 to 10 μm,and typically in the range from about 5 μm to about 100 μm. Further,these manual handling structures, prevent contact by the user oroperator with the relevant surfaces of the device, and therebysignificantly reduce the probability that any surface contamination ofthe device will occur, which contamination could potentially lead toshorting and/or interference with the detection window.

As used herein, the term “microfluidic,” or the term “microscale” whenused to describe a fluidic element, such as a passage, chamber orconduit, generally refers to one or more fluid passages, chambers orconduits which have at least one internal cross-sectional dimension,e.g., depth or width, of between about 0.1 μm and 500 μm. In the devicesof the present invention, the microscale channels preferably have atleast one cross-sectional dimension between about 0.1 μm and 200 μm,more preferably between about 0.1 μm and 100 μm, and often between about0.1 μm and 20 μm. Accordingly, the microfluidic devices or systems ofthe present invention typically include at least one microscale channel,and preferably at least two intersecting microscale channels disposedwithin a single body structure.

The body structure typically comprises an aggregation of separate parts,e.g., capillaries, joints, chambers, layers, etc., which whenappropriately mated or joined together, form the microfluidic device ofthe invention, e.g., containing the channels and/or chambers describedherein. Typically, the microfluidic devices described herein willcomprise a top portion, a bottom portion, and an interior portion,wherein the interior portion substantially defines the channels andchambers of the device. In preferred aspects, the bottom portion willcomprise a solid substrate that is substantially planar in structure,and which has at least one substantially flat upper surface. A varietyof substrate materials may be employed as the bottom portion. Typically,because the devices are microfabricated, substrate materials willgenerally be selected based upon their compatibility with knownmicrofabrication techniques, e.g., photolithography, wet chemicaletching, laser ablation, air abrasion techniques, injection molding,embossing, and other techniques. The substrate materials are alsogenerally selected for their compatibility with the full range ofconditions to which the microfluidic devices may be exposed, includingextremes of pH, temperature, salt concentration, and application ofelectric fields. Accordingly, in some preferred aspects, the substratematerial may include materials normally associated with thesemiconductor industry in which such microfabrication techniques areregularly employed, including, e.g., silica based substrates such asglass, quartz, silicon or polysilicon, as well as other substratematerials, such as gallium arsenide and the like. In the case ofsemiconductive materials, it will often be desirable to provide aninsulating coating or layer, e.g., silicon oxide, over the substratematerial, particularly where electric fields are to be applied.

In additional preferred aspects, the substrate materials will comprisepolymeric materials, e.g., plastics, such as polymethylmethacrylate(PMMA), polycarbonate, polytetrafluoroethylene (TEFLON™),polyvinylchloride (PVC), polydimethylsiloxane (PDMS), polysulfone, andthe like. Such substrates are readily manufactured from microfabricatedmasters, using well known molding techniques, such as injection molding,embossing or stamping, or by polymerizing the polymeric precursormaterial within the mold. Such polymeric substrate materials arepreferred for their ease of manufacture, low cost and disposability, aswell as their general inertness to most extreme reaction conditions.Again, these polymeric materials may include treated surfaces, e.g.,derivatized or coated surfaces, to enhance their utility in themicrofluidic system, e.g., provide enhanced fluid direction, e.g., asdescribed in U.S. Pat. No. 5,885,470, and which is incorporated hereinby reference in its entirety for all purposes.

The channels and/or chambers of the microfluidic devices are typicallyfabricated into the upper surface of the substrate, or bottom portion,using the above described microfabrication techniques, as microscalegrooves or indentations. The lower surface of the top portion of themicrofluidic device, which top portion typically comprises a secondplanar substrate, is then overlaid upon and bonded to the surface of thebottom substrate, sealing the channels and/or chambers (the interiorportion) of the device at the interface of these two components. Bondingof the top portion to the bottom portion may be carried out using avariety of known methods, depending upon the nature of the substratematerial. For example, in the case of glass substrates, thermal bondingtechniques may be used which employ elevated temperatures and pressureto bond the top portion of the device to the bottom portion. Polymericsubstrates may be bonded using similar techniques, except that thetemperatures used are generally lower to prevent excessive melting ofthe substrate material. Alternative methods may also be used to bondpolymeric parts of the device together, including acoustic weldingtechniques, or the use of adhesives, e.g., UV curable adhesives, and thelike.

In accordance with the present invention, the microfluidic devicesand/or systems include a manual handling structure. By “manual handlingstructure” is meant a structural element that is attached to or anintegral part of the microfluidic device or system, which facilitatesthe manual handling of the device or system, and prevents excess contactbetween the handler and the microfluidic device, per se. The holdingstructures may be fabricated as an integrated portion of themicrofluidic device, e.g., as an extension of the device's bodystructure, or alternatively may comprise a separately fabricatedstructure that is attached to the microfluidic device, eitherpermanently or removably. In the latter instance, the handling structuremay be fabricated as a portion of a separate holder assembly, into whichthe microfluidic device is permanently or removably inserted. In eitherevent, the microfluidic device is securely inserted into the holderassembly. Typically, such holding structures will be fabricated from apolymeric material, e.g., polystyrene, polypropylene, or the otherpolymeric materials described herein. These materials are selected,again for their inertness to the various reagents, temperatures or otherconditions to which the overall device might be subjected.

By reducing or preventing contact with the device, the manual handlingstructures described herein, serve to prevent fouling of the deviceresulting from excess handling of the device. For example, in a firstaspect, the manual handling structures prevent the deposition of debris,e.g., dirt, dust or other detritus, on the surface of the deviceresulting from manual contact with that surface. Such debris can bedeposited within the wells or reservoirs of the device, and canpotentially clog or otherwise interfere with flow within the channels ofthe device. This is a particular hazard for devices which include largenumbers of ports or reservoirs, providing greater opportunity for debristo find is way into the channel elements. These include those devicesintended for the analysis of multiple samples, which devices can includeupwards of 8, 12, 16 and even 18 or more reservoirs or ports.

As noted previously, the manual handling structures, as described interms of the present invention, provide the most significant advantagein microfluidic devices which utilize either or both of electricalmaterial direction/transport systems, and optical detection methods andsystems.

In preferred aspects, the devices, methods and systems described herein,employ electrokinetic material transport systems, and preferably,controlled electrokinetic material transport systems. As used herein,“electrokinetic material transport systems” include systems whichtransport and direct materials within an interconnected channel and/orchamber containing structure, through the application of electricalfields to the materials, thereby causing material movement through andamong the channel and/or chambers, i.e., cations will move toward thenegative electrode, while anions will move toward the positiveelectrode.

Such electrokinetic material transport and direction systems includethose systems that rely upon the electrophoretic mobility of chargedspecies within the electric field applied to the structure. Such systemsare more particularly referred to as electrophoretic material transportsystems. Other electrokinetic material direction and transport systemsrely upon the electroosmotic flow of fluid and material within a channelor chamber structure which results from the application of an electricfield across such structures. In brief, when a fluid is placed into achannel which has a surface bearing charged functional groups, e.g.,hydroxyl groups in etched glass channels or glass microcapillaries,those groups can ionize. In the case of hydroxyl functional groups, thisionization, e.g., at neutral pH, results in the release of protons fromthe surface and into the fluid, creating a concentration of protons atnear the fluid/surface interface, or a positively charged sheathsurrounding the bulk fluid in the channel. Application of a voltagegradient across the length of the channel, will cause the proton sheathto move in the direction of the voltage drop, i.e., toward the negativeelectrode.

“Controlled electrokinetic material transport and direction,” as usedherein, refers to electrokinetic systems as described above, whichemploy active control of the voltages applied at multiple, i.e., morethan two, electrodes. Rephrased, such controlled electrokinetic systemsconcomitantly regulate voltage gradients applied across at least twointersecting channels. Controlled electrokinetic material transport isdescribed in Published PCT Application No. WO 96/04547, to Ramsey, whichis incorporated herein by reference in its entirety for all purposes. Inparticular, the preferred microfluidic devices and systems describedherein, include a body structure which includes at least twointersecting channels or fluid conduits, e.g., interconnected, enclosedchambers, which channels include at least three unintersected termini.The intersection of two channels refers to a point at which two or morechannels are in fluid communication with each other, and encompasses “T”intersections, cross intersections, “wagon wheel” intersections ofmultiple channels, or any other channel geometry where two or morechannels are in such fluid communication. An unintersected terminus of achannel is a point at which a channel terminates not as a result of thatchannel's intersection with another channel, e.g., a “T” intersection.In preferred aspects, the devices will include at least threeintersecting channels having at least four unintersected termini. In abasic cross channel structure, where a single horizontal channel isintersected and crossed by a single vertical channel, controlledelectrokinetic material transport operates to controllably directmaterial flow through the intersection, by providing constraining flowsfrom the other channels at the intersection. For example, assuming onewas desirous of transporting a first material through the horizontalchannel, e.g., from left to right, across the intersection with thevertical channel. Simple electrokinetic material flow of this materialacross the intersection could be accomplished by applying a voltagegradient across the length of the horizontal channel, i.e., applying afirst voltage to the left terminus of this channel, and a second, lowervoltage to the right terminus of this channel, or by allowing the rightterminus to float (applying no voltage). However, this type of materialflow through the intersection would result in a substantial amount ofdiffusion at the intersection, resulting from both the natural diffusiveproperties of the material being transported in the medium used, as wellas convective effects at the intersection.

In controlled electrokinetic material transport, the material beingtransported across the intersection is constrained by low level flowfrom the side channels, e.g., the top and bottom channels. This isaccomplished by applying a slight voltage gradient along the path ofmaterial flow, e.g., from the top or bottom termini of the verticalchannel, toward the right terminus. The result is a “pinching” of thematerial flow at the intersection, which prevents the diffusion of thematerial into the vertical channel. The pinched volume of material atthe intersection may then be injected into the vertical channel byapplying a voltage gradient across the length of the vertical channel,i.e., from the top terminus to the bottom terminus. In order to avoidany bleeding over of material from the horizontal channel during thisinjection, a low level of flow is directed back into the side channels,resulting in a “pull back” of the material from the intersection.

In addition to pinched injection schemes, controlled electrokineticmaterial transport is readily utilized to create virtual valves whichinclude no mechanical or moving parts. Specifically, with reference tothe cross intersection described above, flow of material from onechannel segment to another, e.g., the left arm to the right arm of thehorizontal channel, can be efficiently regulated, stopped andreinitiated, by a controlled flow from the vertical channel, e.g., fromthe bottom arm to the top arm of the vertical channel. Specifically, inthe ‘off’ mode, the material is transported from the left arm, throughthe intersection and into the top arm by applying a voltage gradientacross the left and top termini. A constraining flow is directed fromthe bottom arm to the top arm by applying a similar voltage gradientalong this path (from the bottom terminus to the top terminus). Meteredamounts of material are then dispensed from the left arm into the rightarm of the horizontal channel by switching the applied voltage gradientfrom left to top, to left to right. The amount of time and the voltagegradient applied dictates the amount of material that will be dispensedin this manner.

Although described for the purposes of illustration with respect to afour way, cross intersection, these controlled electrokinetic materialtransport systems can be readily adapted for more complex interconnectedchannel networks, e.g., arrays of interconnected parallel channels.

The incorporation of manual handling structures prevents the depositionof fluids, dirt and oils from the operators hands or other handlingequipment, which may affect the level of condensation on the surface ofthe microfluidic device. Such condensation can eliminate the electricalisolation between adjacent wells on the microfluidic device, effectivelyshorting out the material transport system. Additional measures may alsobe provided to avoid this condensation, including application ofhydrophobic coatings on the surface of the device, e.g.,polytetrafluoroethylene (TEFLON™), and the like.

Also as noted previously, the microfluidic devices incorporating manualhandling structures are particularly advantageous where thesemicrofluidic devices incorporate or are utilized with optical detectionsystems. Such devices typically include, fabricated into theirstructure, an optical detection window fabricated across one of theplurality of channels within the device, whereby an analyte travelingwithin that channel is detected by virtue of an optical characteristicor label. The detection window may comprise a portion of the substratematerial, where that material is transparent, e.g., glass, quartz, ortransparent polymeric substrates. Alternatively, for opaque substrates,or substrates which have excessive background signals (e.g.,fluorescence), detection windows fabricated from an appropriatetransparent material, e.g., glass, quartz and the like, may beintroduced into the structure of the device, across the channel inquestion.

In operation, an optical detector is positioned adjacent to thedetection window whereby the detector senses the presence or absence ofthe optical characteristic within the channel. Examples of suchoptically detectable labels include, e.g., colored labels, colloidlabels, fluorescent labels, e.g., fluorescein, rhodamine, etc., andchemiluminescent labels. The optical detector may be any of a variety ofoptical detection systems, e.g., fluorescent, colorimetric or videodetection systems. For example, for fluorescence based analyses, theoptical detector will typically include an excitation light source,e.g., a laser or LED, collection optics for collecting fluorescence fromthe sample and separating that fluorescence from the reflectedexcitation light, and detectors, such as photodiodes and/orphotomultiplier tubes, for detecting, quantifying and/or recording theamount of fluorescence from the channel. Alternate detectors include,e.g., CCDs (charged coupled devices) disposed adjacent the channel andcoupled to monitoring/recording equipment, for monitoring and recordingthe analyte level in the channel.

Because these devices and systems are used in relatively preciseanalyses, any interference with the optical detection of analytes withinthe device can have substantial detrimental effect on the results ofsuch analyses. In particular, any dirt, oil or other debris whichdeposits upon the detection window can interfere with the accuratedetection of analyte within the channel. The manual handling structuresof the present invention provide a means of handling these deviceswithout contacting the detection window, thereby reducing theprobability of any such optical contamination occurring.

In addition to the foregoing, and as noted above, the manual handlingstructures described herein are also particularly useful in conjunctionwith very small scale microfluidic devices. For example, in preferredaspects, the handling structures are provided on microfluidic devicesthat have internal, intersecting channel networks disposed within aplanar body structure, where the entire microscale channel network ofthe device falls, i.e., the layout of intersecting channels, within avery small area of the planar device structure which area is typicallyless than 6 cm², preferably less than 5 cm², more preferably less than 4cm², still more preferably less than 3 cm², and often, less than 2 cm²or even 1 cm². Thus, typically, all of the channels of the device arefabricated into the surface of the lower substrate within a regionhaving the area described. In the case of rectangular or square shapeddevices, the layout of the intersecting channel structure will typicallyfall within a region having dimensions less than from about 2.5 cm byabout 2.5 cm, preferably less than about 2 cm by about 2 cm, morepreferably, less than about 1.5 cm by about 1.5 cm, and in some cases,less than about 1 cm by about 1 cm.

One example of a manual handling structure according to the presentinvention is shown in FIG. 1. As shown the microfluidic system 100includes a microfluidic substrate 102, mounted in a holder assembly 104.As shown, the microfluidic device includes within its structure, aplurality of intersecting channels 112 which include at theirunintersected termini, a plurality of reservoirs, wells or ports 114 forintroduction of fluids into the interior portion of the device, as wellas providing electrical contact/access to the fluid within the channels.A detection window 116 is also shown disposed across one f the channels112, which detection window is capable of transmitting an optical signalfrom the channel to a detector. The holder assembly shown, comprises aplanar structure having a first surface with a cavity disposed therein.The cavity 106 is sized or adapted to fit the substrate in a secure,fixed fashion, e.g., such that the device does not freely fall out ofthe holder assembly, e.g., when inverted. Typically, an aperture isprovided through the holder assembly such that when thesubstrate/microfluidic device is inserted into the holder, the detectionwindow 112 is placed over the aperture. This allows the freetransmission of light through the detection window 116 and the remainderof the device for optical detection. For example, a light source may beplaced above the substrate and directed at one of the channels in thedevice. Light passing through the channel and the device then proceedsthrough the aperture in the holder assembly and reaches a detectordisposed below the device. In some instances, the substrate may bepermanently affixed to the holder assembly, e.g., using adhesives, or inthe case of polymeric substrates, through the use of solvent bonding,acoustic welding or thermal bonding techniques.

The holder assembly extends in one dimension from an edge of thesubstrate/microfluidic device, i.e., from the edge of the cavity intowhich the microfluidic device is inserted, providing a flat planarsurface 108, upon which are fabricated a plurality of raised ridges 110.The surface 106 and ridges 108 provide a gripping surface for manuallyhandling the microfluidic device substantially without actuallycontacting the surface of the substrate/microfluidic device, i.e.,contacting less than 25% of the surface, preferably, less than 10% ofthe surface and often less than 5% of the substrate surface. A varietyof other surface textures may similarly or alternatively be providedupon the surface of the handling structure in the place of raisedridges, such as knurling, raised bumps, surface roughing and the like.Similarly, rubber holder assemblies, or rubber handling structuresattached to the holder assemblies may also be used to provide a suitablegripping surface, e.g., particularly in wet processes.

Another example of manual handling structure according to the presentinvention, is shown from a perspective view in FIG. 2. As shown, theplanar microfluidic substrate 102 (channels and reservoirs not shown),is again inserted into a holder assembly 204 such that at least its topsurface is exposed, e.g., providing access to the ports/reservoirs, forfluid introduction and electrode access. Typically, the bottom surfaceof the device is also exposed, i.e., not covered by the holder assembly.This permits access to the bottom surface of the device, i.e., opticalaccess for the detector, thermal access for a heating or cooling elementor heat sink, e.g., a resistive heater, peltier cooler or the like. Theholder assembly includes inwardly tapered or inset edges 206, atopposing edges of the device, for manually holding the overall devicewithout substantially contacting either of the top or bottom surfaces ofthe microfluidic device. Although not shown, the edges of the device mayalso include raised ridges to provide an adequate gripping surface forthe overall device. In addition, although the substrate portion of thedevice is shown having a particular shape, e.g., a planar rectangle orsquare, it will be readily appreciated that a variety of substrateshapes may be used, including disks, i.e., circles, triangles etc. Assuch, the above description, in referring to a device having twoopposite edges, also encompasses those embodiments having edges that aresubstantially opposite to each other in the planar structure despite thefact that such a device may not include two separate and distinct edges.For example, although a device having a planar, circular shape has butone edge, two portions of that edge may be opposite each other in theplanar structure of the device, and would therefor fall within thedescription provided herein for a structure having at least two opposingor opposite edges.

A similar, related example of a manual handling structure according tothe present invention is shown in FIG. 3, from a perspective view (FIG.3A), a top view (FIG. 3B) and a bottom view (FIG. 3C). Again, as shown,the microfluidic substrate 102 (reservoirs and channels not shown) isinserted into a holder assembly 304, such that the top and bottomsurfaces 306 and 308 of the substrate are exposed. As with the holderassembly shown in FIG. 2, the device shown in FIG. 3 also includesbeveled or chamfered edges 310 as the manual handling structure. Asshown, the beveled or chamfered edges 310 of the holder assembly onlyextend up a portion of the side edges 312 of the assembly. This permitsthe added advantage of providing a lip portion of the device whichallows one to lift the overall device when it is sitting flatly on aflat surface, or mounted in a further holding structure, e.g., a nestingwell in a controller, scanner, or fabrication device. A related designfor a microfluidic device housing, including a manual handling structureis shown in FIG. 4. Again, although FIG. 4 illustrates a housing intowhich a separate device is inserted, it will be readily appreciated thatthe housing element may be manufactured as an integral part of thedevice, e.g., as an extended portion of the body structure of thedevice.

In addition to the manual handling structures described above, thedevices of the present invention may also include other structuralelements to facilitate their handling and use. For example, the devicesmay include alignment structures to ensure proper insertion of thedevice into the instrumentation used in the device's operation, e.g.,electrical controllers, detectors, filling systems, sample introductionsystems and related instrumentation. Alignment of the microfluidicdevices within these instruments is important to ensure the properalignment of the device for: (1) receiving electrodes, for electricalfluid direction systems; (2) for properly positioning the reservoirs forintroduction of fluids and samples, e.g., for receipt of the fluidintroduction conduits, i.e., pipette tips; and (3) for proper alignmentof the detection window of the device in front of the detector. Suchalignment structures may comprise one or more of a number of differentstructural elements. For example, alignment holes or pins may beprovided upon the device such that the holes or pins align withcorresponding, complementary pins or holes on the instrumentation.Alternatively, sides or edges of the device may incorporate structuralfeatures, e.g., notches, tabs, cropped corners, bevels, ridges and thelike, which are complementary to structural features on theinstrumentation, e.g., in a nesting well for the controller and/orscanning device.

For those devices which are intended for use with multiple samples,e.g., having multiple sample introduction reservoirs, wells or ports,the devices may also include indexing elements, for identifying thevarious sample introduction wells. For example, in the case ofrectangular or square devices, such indexing elements can include marks,notches, or alphanumeric symbols disposed along one edge of the device(on one axis), e.g., on the device itself or on the holder assemblyadjacent to the device, which marks or symbols are aligned with each rowof sample reservoirs or wells. A second set of marks or symbols may beprovided on a second edge of the device adjacent the first (on the otheraxis).

By reducing the actual contact the user has with the microfluidicdevice, as well as ensuring the proper use of the device, all of theabove described features cooperate to prevent or reduce the possibilityof operator mishandling of the microfluidic devices described herein,and particularly that mishandling which results from excessive contactwith the relevant surfaces of the device.

Although the present invention has been described in some detail by wayof illustration and example for purposes of clarity and understanding,it will be apparent that certain changes and modifications may bepracticed within the scope of the appended claims. All publications,patents and patent applications referenced herein are herebyincorporated by reference in their entirety for all purposes as if eachsuch publication, patent or patent application had been individuallyindicated to be incorporated by reference.

What is claimed is:
 1. A microfluidic device, comprising: a planar bodystructure; at least a first channel network comprising intersectingchannels disposed within the body structure; wherein the first channelnetwork is contained within an area of the planar body structure that isless than about 6 cm²; and a holder assembly configured to receive thebody structure, the holder assembly having at least one aperturedisposed therethrough from an upper surface to a lower surface thereof,and wherein the body structure is fixedly mounted to the holderassembly.
 2. The microfluidic device of claim 1, wherein the firstchannel network is contained within an area of the planar body structurethat is less than about 5 cm².
 3. The microfluidic device of claim 1,wherein the first channel network is contained within an area of theplanar body structure that is less than about 4 cm².
 4. The microfluidicdevice of claim 1, wherein the first channel network is contained withinan area of the planar body structure that is less than about 3 cm². 5.The microfluidic device of claim 1, wherein the first channel network iscontained within an area of the planar body structure that is less thanabout 2 cm².
 6. The microfluidic device of claim 1, wherein the firstchannel network is contained within an area of the planar body structurethat is less than about 1 cm².
 7. The microfluidic device of claim 1,wherein the body structure comprises a square or rectangular shapehaving dimensions less than from about 2 cm by about 2 cm.
 8. Themicrofluidic device of claim 1, wherein the body structure comprises asquare or rectangular shape having dimensions less than from about 1.5cm by about 1.5 cm.
 9. The microfluidic device of claim 1, wherein thebody structure comprises a square or rectangular shape having dimensionsless than from about 1 cm by about 1 cm.
 10. The microfluidic device ofclaim 1, wherein the body structure comprises a plurality of reservoirsdisposed in a surface of the body structure, the plurality of reservoirsbeing in fluid communication with the at least first channel network.11. The microfluidic device of claim 10, wherein the plurality ofreservoirs are in communication with unintersected termini of theintersecting channels.
 12. The microfluidic device of claim 1, wherein:the body structure comprises upper and lower planar substrate layers;the intersecting channels of the first channel network are fabricated asa plurality of grooves on a surface of the lower substrate; and theupper planar substrate layer is overlaid and bonded to the lower planarsubstrate layer to seal the plurality of grooves to form the firstchannel network.
 13. The microfluidic device of claim 12, wherein atleast one of the upper and lower planar substrate layers is selectedfrom a group consisting of glass, quartz, and a polymeric material. 14.The microfluidic device of claim 1, wherein the holder assemblycomprises a cavity, the cavity being sized to fixedly receive the bodystructure.
 15. The microfluidic device of claim 1, wherein the holderassembly comprises at least a first alignment structure for aligning themicrofluidic device on a detector instrument.
 16. The microfluidicdevice of claim 1, wherein the holder assembly comprises a polymericholder assembly.